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Xiaojiao Xu,1,2 Yuheng Shan,3 Yuying Cen,2,4 Jiahua Zhao,2,4 Xiaosa Yang,2,4 Rui Liu,1,2 Qingche Tan,2 Yubao Ma,2 Mianwang He,2 Jiatang Zhang,1,2,4 Fei Yang,2 Shengyuan Yu2 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Neurology, Characteristic Medical Centre of People’s Armed Police Force, Tianjin, 300162, People’s Republic of China; 4Medical School of Chinese PLA, Beijing, 100853, People’s Republic of ChinaCorrespondence: Jiatang Zhang; Fei Yang, Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13601380322 ; Tel +86 13910973120, Email zjt1128@aliyun.com; yangfeiyanbian@163.comPurpose: Listeria monocytogenes infections are rare in the central nervous system (CNS) and frequently difficult-to-diagnose. Our goal is to assess CNS listeriosis patients’ clinical characteristics, diagnosis, treatment, and prognosis.Patients and Methods: Patients with CNS listeriosis admitted to the Department of neurology, the first medical center of the Chinese PLA general hospital, were enrolled in this study from March 2018 to August 2022.Results: This study analyzed eight adults, including five males and three females. The average age of onset was (50.25 ± 11.52) years. The clinical manifestations included fever, headache, altered mental status, vomiting, seizures, neck rigidity, hemiplegia and cranial nerve palsies. Cerebrospinal fluid (CSF) tests revealed intracranial hypertension, elevated cell count and protein concentration, and decreased glucose levels. The positive rates of blood and CSF culture were 40% and 28.57%, respectively. All patients underwent CSF metagenomic next-generation sequencing (mNGS), with a 100% positive rate and the specific read number 12– 20394. Magnetic resonance imaging (MRI) exhibited leptomeningitis, meningoencephalitis, and brain abscess, and no specific changes were discovered in two patients. All patients received antibiotic treatment, seven were cured, and one died.Conclusion: Monitoring the proportion of monocytes in blood and mNGS results of CSF can play a crucial role in diagnosing pathogens. Early and sufficient application of two to three sensitive antibiotics with a BBB permeability of 20– 30% for at least 2– 3 months can significantly improve CNS listeriosis prognosis.Keywords: Listeria monocytogenes, central nervous system, CNS, clinical characteristics, treatment, metagenomic next-generation sequencing, mNGS

Zemin Hou,1,2,* Wencheng Zhou,1,2,* Xi Guo,2 Rui Zhong,3 Ao Wang,4 Jiehua Li,4 Ying Cen,1 Chao You,2 Hong Tan,4 Meng Tian2 1Department of Burn and Plastic Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Neurosurgery and Neurosurgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Institute of Blood Transfusion, Chinese Academy of Medical Science & Peking Union Medical College, Chengdu, Sichuan, People’s Republic of China; 4College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Tian, Department of Neurosurgery and Neurosurgery Research Laboratory, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86 28 85164168, Email tianmeng@scu.edu.cnBackground: The main challenge of polymeric micelles as drug delivery systems is that the actual delivery efficiency is not as high as expected, which is closely related with the interactions with the complex biological environments such as blood components, phagocytosis, and biodistribution. Herein, we expect to understand these concerns for the clinically relevant micelles that composed of methoxypolyethylene glycol (MPEG) with identical chain length And poly(ϵ-caprolactone) (PCL) with tunable chain length (PCLn-MPEG) (n=20, 30, and 40) wherein doxorubicin was encapsulated as a model drug.Methods: The doxorubicin-loaded PCLn-MPEG micelles were prepared by a dialysis method and characterized by dynamic light scattering and transmission electron microscopy. The surface PEG density and chain conformation were investigated by dissipative particle dynamics simulation. The stability of the micelles was detected by nanoparticle tracking analysis. The effects of PCL chain length on the blood components, phagocytosis, and biodistribution were assayed in vitro and in vivo.Results: The micelles exhibited spherical morphology with a diameter about 30nm. The PEG chain conformation from “mushroom-like” to “brush-like” was evident. The micelles have no remarkable effect on the red blood cells, blood coagulation, and platelet activation. Interestingly, the protein adsorption was affected and dependent on the chain conformation, with lowest adsorption for PCL30-MPEG, which also has the loWest phagocytosis. The stability of the micelles was in the order of PCL40-MPEG>PCL30-MPEG>PCL20-MPEG which was dependent on the PCL chain length. The micelles mainly accumulated in liver, with the order consistent with their stability, indicating that, besides the phagocytosis, the stability of the micelle plays an important role in biodistribution as well. The related mechanisms were proposed and discussed.Conclusion: Manipulating the PEG/PCL ratio of the micelle is an effective approach to modulate the protein adsorption, phagocytosis, and biodistribution, which may be a prerequisite for clinical applications.Keywords: micelles, blood components, phagocytosis, biodistribution

Yanbo Sun,1,* Jing Luo,2,* Chuan Qian,3,* Lan Luo,3 Manqi Xu,1 Haiyan Min,3 Yunyun Cen1 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First People’s Hospital of Qujing, Qujing, 655000, People’s Republic of China; 3The Second Department of Infection, Yunnan Provincial Infectious Disease Hospital, Kunming, 650301, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunyun CenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374 of Yunnan-Burma Road, Kunming City, Yunnan Province, 650101, People’s Republic of ChinaTel +86-871-63402778Fax +86-871-65361017Email drcenyunyun@163.comHaiyan MinThe Second Department of Infection, Yunnan Provincial Infectious Disease Hospital, Shi’an Highway in Kunming, Kunming City, Kunming, Yunnan Province, 650301, People’s Republic of ChinaTel/Fax +86-871-68728053Email min_haiy23an@126.comObjective: Many studies have suggested that indexes of nutritional status, such as body mass index (BMI), serum albumin (ALB), serum pre-albumin (PA), and hemoglobin, may be used as risk factors for the prognosis of HIV or lymphoma. Therefore, this study aimed to retrospectively analyze and explore the value of nutritional status in the prognostic assessment of patients with AIDS-related lymphoma (ARL).Methods: In this retrospective study, the clinical data of 69 patients with ARL were collected. All patients had a definite diagnosis of non-Hodgkin lymphoma by pathological examination and met the requirements of the Hematopoietic and Lymphocytic Tissue Tumor Classification (2016) established by the World Health Organization. Patients who did not receive standard chemotherapy, those with incomplete medical records, and those with an unclear pathological diagnosis were excluded. The patients were divided into two groups (survival and death) according to the prognostic outcome, and their clinical characteristics and prognoses were discussed by relevant statistical methods.Results: During the three-year follow-up period, 20 (28.99%) patients died, and 49 (71.01%) survived. The one-year cumulative survival rate was 78.26%. A univariate analysis found that the prognosis was associated with the International Prognostic Index (IPI) score, BMI, ALB, PA, and CD4 T lymphocyte count. The Cox risk proportional regression analysis showed that the IPI score, BMI, and PA were the independent risk factors for survival; their combination had a greater ability to forecast the clinical outcome (area under the curve = 0.874, P < 0.001).Conclusion: In this study, at the time of the visit, the patients with ARL tended to be in the advanced stages of disease and, therefore, at high risk of mortality. Therefore, their nutritional status might be of great value to the prognostic assessment. The combination of BMI, PA, and IPI scores could be used for risk stratification and better screening of high-risk patients.Keywords: AIDS-related lymphoma, body mass index, pre-albumin, prognostic factor, retrospective analysis

Yanbo Sun,1,* Jing He,2,* Weiming Li,1,* Shumin Li,1 Yueying Lin,1 Yunyun Cen,1 Yanli Li3 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China; 2The First Department of Infectious Disease, The Third People’s Hospital of Kunming, Kuming, 650041, People’s Republic of China; 3First Department of Pulmonary and Critical Care Medicine, Yan’an Hospital of Kunming City/Yan’an Hospital Affiliated to Kunming Medical University, Yunnan, 650000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunyun CenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374 of Yunnan-Burma Road, Kunming City, Yunnan Province, 650101, People’s Republic of ChinaTel +86-871-63402778Fax +86-871-65361017Email drcenyunyun@163.comObjective: This study was designed to explore the impact of different scoring settings of disease severity on the accuracy of screening by NRS2002.Methods: Patients with severe COVID-19 who were admitted to our hospital from January 26, 2020, to March 16, 2020, were enrolled in this study. The basic data, the scores of the NRS2002 score sheet, and the serum prealbumin (PAB) level when these patients were admitted were collected, and the reflection of NRS2002 scores under different disease severity score settings to abnormal patients was analyzed.Results: 1. When the severity of the disease was set to 0 points, four of the six hospitalized patients with PAB levels below the lower normal limit were not screened out; 2. When the severity was set to 1 point, two patients with COVID-19 who developed to a severe stage during the treatment process were screened out, but three of the six hospitalized patients with PAB levels below the lower normal limit at admission were not screened out; 3. When the severity of the disease of a patient with severe COVID-19 and fever scored 2 points, and that of a patient without fever scored 1 point, two patients with COVID-19 who developed to the severe stage during the treatment process were screened out, and six patients who were hospitalized with PAB levels below the lower normal limit at admission were also screened out.Conclusion: When the severe degree of patients with COVID-19 and fever is rated as 2 points, and that of the patients without fever is rated as 1 point, it can more accurately reflect the severity degree of patients with undernourishment.Keywords: novel coronavirus pneumonia, severe patients, nutritional risk, NRS2002, prealbumin

Zhenyu Zhang,1 Lihui Cheng,2 Ru Wang,1 Ying Cen,1 Zhengyong Li1 1Department of Aesthetic Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Triamcinolone acetonide (TAC) is used frequently in the treatment of keloid scars, but has presented controversial results. In this study, we aim to evaluate the effectiveness of TAC compared with other common therapies used in keloid treatment. Methods: MEDLINE, Embase, Web of Science and the Cochrane Library databases were searched until January 2018. Key data were extracted from eligible randomized controlled trials. Both pairwise and network meta-analyses were conducted for synthesizing data from eligible studies. Results: Ten randomized controlled trials were included in this meta-analysis. The relative risk of keloids associated with seven adjuvants was analyzed, including placebo, pulsed dye laser (PDL), 5-fluorouracil (5-FU), silicone, verapamil, TAC+5-FU and TAC+5-FU+PDL. Patients treated with the following adjuvants appeared to not have significantly reduced risk of keloid in relation to those treated with TAC: placebo (OR=1.86, 95% CI 1.12–2.61), PDL (OR=1.32, 95% CI 0.53–3.30), 5-FU (OR=1.13, 95% CI 0.48–2.68), silicone (OR=1.28, 95% CI 0.59–2.78), verapamil (OR=1.86, 95% CI 0.67–5.14), TAC+5-FU (OR=0.77, 95% CI 0.38–1.58) and TAC+5-FU+PDL (OR=0.80, 95% CI 0.16–4.03). The surface under the cumulative ranking curve values for each adjuvant were as follows: TAC, 59.9%; placebo, 17.4%; PDL, 46.3%; 5-FU, 48.9%; silicone, 56.2%; verapamil, 84.7%; TAC+5-FU, 68.5% and TAC+5-FU+PDL, 18.1%. Conclusion: There were no differences between the efficacy of TAC and other common therapies in keloid treatment. TAC also acts as an effective alternative modality in the prevention and treatment of keloids. Incorporating adjuvants particularly verapamil appeared to be significantly associated with a decreased risk of keloids. Keywords: keloid, triamcinolone acetonide, randomized controlled trial, network meta-analysis

Ru Wang, Junjie Chen, Zhenyu Zhang, Ying CenDepartment of Burn and Plastic Surgery, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaBackground: Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-β1 (TGF-β1)/Smad activation in keloid fibroblasts (KFs). However, the role of chymase in the local renin-angiotensin system (RAS) in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids.Methods: We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-β1, interleukin-1β, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors’ treatment.Results: The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-β1, and interleukin-1β in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors.Conclusion: This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids.Keywords: pathological scar, chymase, angiotensin II, therapy

Micro‐alloying effects of lanthanum in thermo‐mechanical control process of manganese‐chromium‐molybdenum bainite rail steel are investigated through experimental simulation and microstructural characterization. The results show that the deformation strengthening effect is fully exerted by thermo‐mechanical control process in steel containing 0.015 % lanthanum. Finally a kind of multi‐layer bainite ferrite microstructure featured by 3.5 μm blocks, 0.41 μm plates and 108 nm sub‐plates with ultrafine sub‐subunits and 55 nm θ‐M3C inside is achieved, which enhances the strength and toughness synergistically. And the nanoscale refinement mechanism of bainite ferrite plates lies in the formation of massive ultrafine sub‐subunits with the average size of 20 nm ×32 nm. Besides, a large number of twinning martensite with the size of 2 nm to 20 nm and high‐density entangled dislocations can be found on the boundaries of ultrafine sub‐subunits. Further, the density of dislocation is increased by 2.92×1014 cm−2 and its contribution to the strength is calculated to be 18 MPa. Moreover, micro‐alloying effects of lanthanum in thermo‐mechanical control process are explored to be that lanthanum enhances the interaction between bainite ferrite plates and dislocations, strengthens the entanglement of carbon and θ‐M3C with dislocations, and promotes the pinning effect of θ‐M3C on ultrafine subunits. [ABSTRACT FROM AUTHOR]

BackgroundMigraine is a common primary headache that has a significant impact on patients’ quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background.ObjectiveThe aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort.MethodsIn this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom’s MALDI-TOF iPLEX platform.ResultsIn univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS).ConclusionThe study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

[Objective] To explore the mechanism of Cyclobalanopsis glauca seedlings adapting to the drought-rehydration environment in Karst area, China, using the seedlings of C. glauca as materials, which providds theoretical basis for vegetation restoration and artificial afforestation in the region. [Methods] Water control experiments in pots were carried out. The effects of four different drought treatments, including control (-0.1 MPa), mild drought (-0.5 MPa), moderate drought (-0.9 MPa), severe drought (-1.5 MPa), and rehydration treatments, on photosynthesis, chlorophyll fluorescence, and anatomical structure of leaves were studied. [Results] (1) With the increase in drought stress intensity, the leaf relative water content, water potential, net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), and intercellular CO2 concentration (Ci) were significantly decreased, while stomatal limitation (Ls) was increased significantly. Photosynthetic parameters under mild stress and instantaneous water use efficiency (WUE) under mild and moderate drought stress were not significantly affected. After rehydration, leaf water parameters, Pn, Tr, Gs, Ci, and WUE under drought stress were higher than those before rehydration, while Ls was lower than those before rehydration. The leaf water conditions and photosynthetic parameters under mild drought stress were better than those of the control after rehydration. Only Ls under moderate drought stress did not recover to the level of the control after rehydration. Neither leaf water content nor photosynthetic parameters under severe drought stress were recovered to the level of the control after rehydration. (2) With the increase in drought stress intensity, the initial fluorescence (Fo) of leaves were increased significantly, while the maximum fluorescence (Fm), maximum photochemical quantum yield (Fv/Fm) and potential photochemical efficiency (Fv/Fo) of leaves were decreased significantly. There were significant differences in these parameters between mild drought stress and control. After rehydration, Fm, Fv/Fm, and Fv/Fo under drought stress were higher than those before rehydration, whereas Fo was slightly lower than that before rehydration. All the chlorophyll fluorescence parameters after rehydration under mild stress recovered to or better than those of the control. Fo under moderate and severe drought stress did not return to the control level after rehydration, and Fv/Fm under severe stress was only 0.75 after rehydration. (3) With the increase in drought stress, leaf thickness, upper and lower epidermis thickness, stomatal density, and main vein conduit diameter were increased significantly, the length and width of stomatal apparatus, stomatal opening area, and sponge tissue thickness were decreased significantly, while palisade tissue thickness, ratio of palisade tissue thickness to spongy tissue thickness, and main vein thickness were changed in the order of moderate > mild > control > severe drought stress. After rehydration, only the stomatal opening area and the thickness of main leaf veins under drought stress were increased significantly compared with that before rehydration. After rehydration, the leaf structural parameters under mild drought stress were restored to or better than those of the control. The stomatal opening area after rehydration in moderate drought stress was still significantly lower than that of the control. After rehydration, the stomatal opening area under severe drought stress failed to recover, and the thickness of main veins under severe drought stress was lower than that of the control. [Conclusion] C. glauca seedlings have strong drought tolerant ability and postdrought recovery ability, which are suitable for ecological restoration in Karst area. The seedlings need to be protected from moderate drought stress (-0.9 MPa) in the nurturing stage, to facilitate post-drought recovery.

Objective To explore the effect of skeletal muscle mass on the outcomes of early joint function in patients undergoing total hip arthroplasty. Methods A prospective study was performed on 107 patients who planned to undergo hip arthroplasty for the first time from November 2020 to December 2021 in Army Medical Center of PLA. The demographic data was collected, and nutritional status and pain status were assessed. Skeletal muscle mass was measured by bioelectrical impedance analysis (BIA), and was corrected to the skeletal muscle mass index (SMI) with their height. With follow-up call, the joint function was assessed with Harris Hip Score Scale, and daily living activities was investigated with Activities of Daily Living(ADL) Scale at 1, 3 and 6 months after surgery. The effect of SMI on early rehabilitation after hip arthroplasty was analyzed. According to the diagnostic criteria of the Asian Sarcopenia Working Group 2019, the patients were divided into normal SMI group and reduced SMI group, and postoperative rehabilitation was compared between the 2 groups. Results Pearson correlation analysis showed that SMI was positively correlated with postoperative Harris score and ADL score. Multivariate linear regression model showed that SMI was an influencing factor of Harris score and of ADL score in different periods after surgery, with a standardized regression coefficient of 0.394~0.436 and 0.391~0.461 (P < 0.01), respectively. The incidence of SMI reduction in total hip arthroplasty was 32.71%. The SMI reduction group had significantly larger ratio of needing walk aid instrument for 30 d, but lower postoperative Harris scores and ADL scores when compared with the normal SMI group (all P < 0.01). Conclusion The preoperative SMI of patients undergoing hip arthroplasty independently affects the outcomes of early joint function, and the patients with reduced SMI are the focus population of clinical rehabilitation care.

Aiming at the weak stiffness of the series support mechanism of the partial-face boring machine, poor adaptability of the non-circular TBM section, and difficulties in dealing with the blind area of excavation, a partial-face TBM propulsion mechanism based on the 6-SPS parallel mechanism is designed, and a stiffness prediction model establishment method considering the local flexibility of the platform is proposed. Firstly, the geological conditions is selected, the propulsion reaction force is calculated according to the total thrust prediction model, and the propulsion mechanism is designed. On the basis of inverse kinematics; the rectangular coordinate boundary search method is used to calculate the position workspace of the mechanism. Then, by deriving the micro-displacement mapping between branch chain and the platform, the branch chain is considered, the gravity of the moving platform is regarded as an external load, and the finite element software is used to identify the flexibility coefficient at the contact point between the platform and the branch chain; a semi-analytical static stiffness model of the propulsion mechanism is established, which is verified by the finite element software. Finally, the influence of the local flexibility of the platform on the stiffness performance is compared and analyzed, and the results show that the stiffness model considering the local flexibility of the platform is more accurate. This study provides a theoretical basis for the design and development of the partial-face TBM propulsion mechanism.

We analyze the coal mine accidents since 2008, extract 30 causes of coal mine safety accidents, and construct the coal mine safety production risk factor network by using social network analysis（ＳＮＡ）. Through the point centrality analysis of SNA network, six key risk factors of coal mine safety production, such as inadequate management system, inadequate education and training, low staff quality, inadequate safety technical measures, less safety investment and inadequate safety supervision, are identified. Through the line centrality analysis of SNA network, six key influence paths of coal mine safety production risk are identified. Finally, according to the analysis results of risk key factors and risk influence paths, we put forward targeted suggestions to deal with the risk of coal mine safety production.

In order to clarify the fatigue crack propagation behavior of pearlitic rail, the three-point bending fatigue crack propagation rate of U75V heavy rail steel in rolling state and heat treatment state was measured. The microstructure, lamella, fracture morphology and fatigue crack propagation trajectory of rail were observed by optical microscope, scanning electron microscope and EBSD. The results show that the average distance between fatigue striation of rolled and heat-treated rails is 252.5 nm and 215.4 nm, the fracture surface of rolled rail presents cleavage steps and river patterns, and the river patterns tend to merge.However, the fatigue fracture surface of the heat-treated rail presents a large number of cleavage steps, more microcracks and tear edges, and the river pattern is dominated by tributaries.The fatigue crack growth rate of heat-treated rail is much lower than that of rolled sample, and it is also slow to reach the stage of crack instability.The fatigue crack propagation mode of rolled and heat-treated rail is the mixed propagation mode of transgranular fracture and intergranular fracture dominated by transgranular fracture, the pearlite lamellae spacing of rolled and heat-treated rails is 272.2 nm and 148.4 nm respectively. The pearlite lamellae of heat-treated rails is fine and has various directions, while there are significant pearlite clusters in the heat-treated rail.There are many branch cracks and crack bridges in the crack growth path, which hinders the crack propagation in the heat-treated U75V heavy rail steel, which is an important reason why the fatigue crack propagation rate of the heat-treated rail is lower than that of the rolled rail.

Arsenic is known to cause damage to the body's immune system by inducing epigenetic changes. However, the molecular mechanism of this damage remains elusive. Here, we report that arsenic disrupts the morphology of lymphocytes, decreases cell viability, and results in abnormal proportions of T lymphocyte subsets. Moreover, our results revealed that arsenic can reduce global acetylation of histone H4 at K16 (H4K16 ac) in lymphocytes via decreasing the level of males absent on the first but upregulates mRNA and protein levels of the forkhead/winged-helix box P3 (Foxp3) gene by increasing the acetylation of histone H4 at K16 (H4K16) at the promoter of Foxp3. Finally, arsenic-induced dysfunction of regulatory T cells (Tregs) could be ameliorated by trichostatin A. Our research indicates that arsenic-induced immunosuppressive effect in human lymphocytes may be related to the acetylation of H4K16 at the promoter of Foxp3 and that histone deacetylase inhibitors may play a role in the prevention and treatment of immune injury caused by arsenic. [ABSTRACT FROM AUTHOR]

Metabolomics analysis reveals that inosine monophosphate, a purine metabolite, promotes myelopoiesis and contributes to severe acute pancreatitis in db/db mice.

OBJECTIVE: This study aims at investigating the functional role of CDCA2 (cell division cycle associated 2) in enhancing proliferative and migratory abilities in melanoma by upregulating CCAD1, thus aggravating the progression of melanoma. PATIENTS AND METHODS: CDCA2 levels in melanoma tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Regulatory effects of CDCA2 on proliferative and migratory abilities in melanoma cells were assessed by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), and wound healing assay, respectively. At last, rescue experiments were conducted to explore the involvement of CCAD1 in CDCA2-regulated progression of melanoma. RESULTS: CDCA2 was upregulated in melanoma tissues, especially in those with metastasis. Identically, in vitro level of CDCA2 was upregulated in melanoma cell lines. The knockdown of CDCA2 in A375 and sk-mel-110 cells inhibited the proliferative and migratory abilities. The overexpression of CCAD1 could partially abolish the inhibitory effects of silenced CDCA2 on proliferative and migratory abilities in melanoma. CONCLUSIONS: CDCA2 stimulates proliferative and migratory abilities in melanoma cells by upregulating CCAD1, thus aggravating the malignant progression of melanoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Previous studies have shown that Quinazoline (QNZ) plays extremely important roles in the cellular physiological activity, but it has been rarely examined on cell behavior following intervertebral disc degeneration (IVDD). The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1β-induced nucleus pulposus (NP) cells degeneration in vitro. PATIENTS AND METHODS: NP were isolated cells from human disc samples collected from patients and the IL-1β-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL-1β group (10 μM), QNZ + IL-1β group (containing 10 nM QNZ and 10 μM IL-1β). Then, the cell viability was determined by CCK-8 assay, and the levels of collagen I, collagen II, aggrecan, p16, p53, β-galactosidase (β-gal), antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG), NF-κB/MAPKs signaling-related proteins and inflammatory factors were examined using Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) in NP cells. Finally, the expressions of IL-1β, IL-6, and TNF-a in the cell supernatants were also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: This study showed that IL-1β promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and β-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1β. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKβ, IκBa, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ. CONCLUSIONS: These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NF-κB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future. [ABSTRACT FROM AUTHOR]

The standard consolidation theory suggests that the hippocampus (HPC) is critically involved in acquiring new memory, while storage and recall gradually become independent of it. Converging studies have shown separate involvements of the perirhinal cortex (PRC) and parahippocampal cortex (PHC) in item and spatial processes, whereas HPC relates the item to a spatial context. These 2 strands of literature raise the following question; which brain region is involved in the recall process of item-location associative memory? To solve this question, this study applied an item-location associative (ILA) paradigm in a single-unit study of nonhuman primates. We trained 2 macaques to associate 4 visual item pairs with 4 locations on a background map in an allocentric manner before the recording sessions. In each trial, 1 visual item and the map image at a tilt (-90° to 90°) were sequentially presented as the item-cue and the context-cue, respectively. The macaques chose the item-cue location relative to the context-cue by positioning their gaze. Neurons in the PRC, PHC, and HPC, but not area TE, exhibited item-cue responses which signaled retrieval of item-location associative memory. This retrieval signal first appeared in the PRC, followed by the HPC and PHC. We examined whether neural representations of the retrieved locations were related to the external space that the macaques viewed. A positive representation similarity was found in the HPC and PHC, but not in the PRC, thus suggesting a contribution of the HPC to relate the retrieved location from the PRC with a first-person perspective of the subjects and provide the self-referenced retrieved location to the PHC. These results imply distinct but complementary contributions of the PRC and HPC to recall of item-location associative memory that can be used across multiple spatial contexts.

Extracellular vesicles (EVs), products released by cells in multiple biological activities, are currently widely accepted as functional particles and intercellular communicators. From the orthodox perspective, EVs derived from apoptotic cells (apoEVs) are responsible for cell debris clearance, while recent studies have demonstrated that apoEVs participate in tissue regeneration. However, the underlying mechanisms and particular functions in tissue regeneration promotion of apoEVs remain ambiguous. Some molecules active during apoptosis also function in tissue regeneration triggered by apoptosis, such as caspases. ApoEVs are generated in the process of apoptosis, carrying cell contents to manifest biological effects and possess biomarkers to target phagocytes. The regenerative effect of apoEVs might be due to their abilities to facilitate cell proliferation and regulate inflammation. Such regenerative effect has been observed in various tissues, including skin, bone, cardiovascular system, and kidneys. Engineered apoEVs are produced to amplify the biological benefits of apoEVs, rendering them optional for drug delivery. Meanwhile, challenges exist in thorough mechanistic exploration and standardization of production. In this review, we discussed the link between apoptosis and regeneration, current comprehension of the origination and investigation strategies of apoEVs, and mechanisms in tissue regeneration of apoEVs and their applications. Challenges and prospects are also addressed here.

Flowering time is an important agronomic trait for soybean yield and adaptation. However, the genetic basis of soybean adaptation to diverse latitudes is still not clear. Four NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED 2 (LNK2) homeologs of Arabidopsis thaliana LNK2 were identified in soybean. Three single-guide RNAs were designed for editing the four LNK2 genes. A transgene-free homozygous quadruple mutant of the LNK2 genes was developed using the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9). Under long-day (LD) conditions, the quadruple mutant flowered significantly earlier than the wild-type (WT). Quantitative real-time PCR (qRT-PCR) revealed that transcript levels of LNK2 were significantly lower in the quadruple mutant than in the WT under LD conditions. LNK2 promoted the expression of the legume-specific E1 gene and repressed the expression of FT2a. Genetic markers were developed to identify LNK2 mutants for soybean breeding. These results indicate that CRISPR/Cas9-mediated targeted mutagenesis of four LNK2 genes shortens flowering time in soybean. Our findings identify novel components in flowering-time control in soybean and may be beneficial for further soybean breeding in high-latitude environments.